Yixin‐Shu Capsules Ameliorated Ischemia‐Induced Heart Failure by Restoring Trx2 and Inhibiting JNK/p38 Activation

Abstract

Traditional Chinese medicine has shown great safety and efficacy in the treatment of heart failure (HF), whereas the mechanism remains unclear. In this study, the protective effect of Yixin-shu (YXS) capsules, a conventional medicine for various cardiovascular diseases, against myocardial ischemia-induced HF in rats was systematically investigated by RNA-seq technology. HF rats treated with YXS (0.8 or 1.6 g/kg/d, ig) for 6 weeks had significantly decreased brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and collagen III and attenuated cardiac structure rupture and collagen deposition. Additionally, YXS treatment decreased the levels of interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and lactate dehydrogenase (LDH) and TUNEL-positive rate and the nitrotyrosine staining, but increased levels of glutathione (GSH), total antioxidant capacity (T-AOC) activity, and mitochondrial membrane potential. Further experiments demonstrated that YXS restored Trx2 and inhibited the phosphorylation of JNK and p38, thereby improving cardiac function in the rats with HF. Silencing Trx2 decreased the protection of YXS in the response to H2O2 as evidenced by the increase of caspase-3 activity and decrease of GSH level. Thus, YXS enhanced heart function and decreased myocardial damage through restoring Trx2 and inhibiting JNK and p38 activation in ischemia-induced HF.

Human myocardial mitochondrial oxidative capacity is impaired in mild acute heart transplant rejection

“…These findings expose mitochondrial dysfunction as a potential therapeutic target in ACR, especially considering promising effects of dietary interventions on mitochondrial bioenergetics. 33,34 Just recently, a dipeptidyl peptidase-4 inhibitor and the inhibitor of the sodium-glucose linked transporter 2 ertugliflozin have been shown to improve mitochondrial oxidative phosphorylation, whether these effects can be transferred to mitochondrial dysfunction in ACR is yet unclear. 35,36 Oxidative stress Impaired mitochondrial respiration in patients suffering from HF has been associated with excessive mitochondrial ROS release and a reduced ATP production.…”

“…Our results complement these findings and suggest the translation of alterations in mitochondrial gene regulation in functional alterations. These findings expose mitochondrial dysfunction as a potential therapeutic target in ACR, especially considering promising effects of dietary interventions on mitochondrial bioenergetics 33,34 . Just recently, a dipeptidyl peptidase‐4 inhibitor and the inhibitor of the sodium‐glucose linked transporter 2 ertugliflozin have been shown to improve mitochondrial oxidative phosphorylation, whether these effects can be transferred to mitochondrial dysfunction in ACR is yet unclear 35,36 …”

Guhong Injection Prevents Ischemic Stroke-Induced Neuro-Inflammation and Neuron Loss Through Regulation of C5ar1

“…RNA-seq technology, which is characterized with high sensitivity, high accuracy, and high coverage, is a suitable method to systematically explore the mechanism of multi-component and multi-target traditional Chinese medicine (TCM) ( Zhang et al, 2020b ; Xiang et al, 2021 ). Applying this technology, Huangbai liniment was identified to activated Nrf2 and its downstream antioxidant genes to facilitate wound healing ( Zhang et al, 2020b ) while the Yixin-Shu capsule was identified to upregulate Trx2 and inhibit JNK/p38 activation to halt heart failure ( Xiang et al, 2021 ). In this study, the potential mechanism of GHI against ischemic stroke was comprehensively and systematically explored by taking advantage of RNA-seq technology.…”